脓毒性休克患者死亡风险评估及肾脏替代治疗的探索

发布时间：2018-04-17 04:16

本文选题：脓毒性休克 + 急性肾损伤　；参考：《南京医科大学》2016年博士论文

【摘要】：第一部分脓毒性休克患者临床分析及死亡风险评估目的:脓毒性休克(Septic shock)及其导致的多脏器功能障碍综合征(Multiple organ dysfunction syndrome,MODS)是重症患者的主要死亡原因,许多患者未能得到救治即死亡于早期危险阶段。本章研究对临床数据进行分析和整合,探索能够评估脓毒性休克患者死亡风险的临床指标。方法:纳入2009年1月至2014年12月198例脓毒性休克患者的临床数据。根据患者死亡时间的分布规律,将患者分为早期死亡组(5天内死亡)、后期死亡组(6-28天内死亡)及生存组(28天生存)。比较三组患者一般特征、临床和实验室参数,分析各参数对患者死亡及死亡时间的影响;探究导致患者死亡的独立危险因素,由此构建死亡风险模型,ROC曲线验证其适用性。结果:相比于后期死亡及生存的患者,早期死亡患者具有低收缩压(P0.001)、低舒张压(P0.001)、低白细胞(P=0.011)、低白蛋白(P=0.009)及显著降低的PH值(P0.001)。28天内死亡的患者合并急性肾损伤(Acute kidney injury,AKI)(P=0.037)、糖尿病(P=0.042)、冠心病(P=0.049)及需要机械通气(P0.001)的百分率显著高于生存患者。相比于生存者,28天内死亡者在休克发生时具有低体温(P0.001)、高呼吸频率(P=0.010)、高尿酸(P=0.002)、延长的活化部分凝血酶原时间(activatedpartial thromboplastin time,APTT)(P=0.001)、高乳酸(P0.001)及明显升高的急性生理及慢性健康状况评估(Acute physiology and chronic health evaluation,APACHE Ⅱ)(P0.001)和序贯性组织衰竭评估(sequential organ failure assessment,SOFA)评分(P0.001);Cox比例风险模型多因素分析发现:血尿酸(HR=1.001,P=0.037)、PH 值(HR=0.089,P0.001)、APTT(HR=1.012,P=0.001)和血乳酸水平(HR=1.088,P=0.016)为患者死亡的独立影响因子。联合上述4个参数建立死亡风险模型,ROC曲线验证发现:死亡风险模型曲线下面积(AUC)为0.726、敏感性76.5%、特异性59.2,优于SOFA评分(AUC为0.671,敏感性68.6%,特异性54.1%)及APACHE Ⅱ评分(AUC为0.630,敏感性68.6%,特异性54.1%)。结论:脓毒性休克发生时,出现明显低血压、低白细胞、低白蛋白血症及迅速发生失代偿性酸中毒的患者可能处于早期死亡的危险阶段,而明显的低体温、高呼吸频率、高尿酸、APTT延长、高乳酸及明显升高的APACHEⅡ和SOFA评分提示了疾病的严重性;合并AKI、糖尿病、冠心病及需要机械通气患者死亡风险较大;以血尿酸、PH值、APTT和血乳酸联合建立风险模型对脓毒性休克患者死亡有预警作用。第二部分脓毒性休克患者肾脏替代治疗及开始时机的探索目的:比较行肾脏替代治疗(Renal replacement treatment,RRT)与未行RRT患者的一般特征、临床和实验室参数,观察RRT在脓毒性休克治疗中的应用现状,评估RRT对预后的影响;分析行RRT死亡患者与生存患者临床参数的差异,探讨脓毒性休克患者RRT开始时机对患者预后的影响。方法:纳入第一部分中198例脓毒性休克患者,其中行RRT患者87例,未行RRT患者111例,分析两组患者28天死亡率及死亡时间,比较其临床和实验室参数的差异,Cox比例风险模型多因素校正分析RRT对预后的影响;分析行RRT的死亡患者和生存患者临床和实验室参数,依据有统计学意义的参数及AKIN分级、休克发生至RRT开始的时间,将患者分为不同层次,分层分析患者死亡率与生存率的差别。结果:行RRT患者早期死亡率明显低于未行RRT者(P0.001),但两组患者28天死亡率相似(P=0.738);与未行RRT患者相比,行RRT患者更多合并AKI(P0.001)、肿瘤(P=0.038)、冠心病(P=0.021)及充血性心衰(P=0.049),更多非手术患者行RRT(P=0.005);行RRT者APACHEⅡ评分明显高于未行RRT患者(P0.001);Cox比例风险模型多因素分析发现RRT是有利于患者恢复的因素(β=-1.125,HR=0.325,95%可信区间 0.182-0.580,P0.001)。分层分析显示:随着 PH 值的下降(r=-3.840,P0.001)及 APACHEⅡ(r=3.793,P0.001)和SOFA评分的升高(r=7.143,P0.001),死亡率呈现增加趋势;脓毒性休克发生后RRT开始时间与28天死亡呈正相关(r=3.369,P=0.001);休克发生至RRT开始时间的延迟是患者死亡的独立危险因素(β=0.540,HR=1.175,P=0.031)。结论:脓毒性休克行RRT的患者病情更加危重,RRT是有利于患者恢复的治疗方法;行RRT时,PH值明显下降及APACHE Ⅱ和SOFA评分的增高的患者预后不良;休克发生后及早开始RRT有利于患者预后的改善。第三部分肾脏替代治疗的模式对脓毒性急性肾损伤预后的影响目的:脓毒性AKI治疗中,连续性肾脏替代治疗(Continuous renal replacement treatment,CRRT 是否优于间歇性肾脏替代治疗(Intermittent renal replacement treatment,IRRT),目前仍不清楚。我们比较了连续性静脉静脉血液滤过(Continuous venovenous hemofiltration,CVVHF)(连续治疗超过 72 小时)与每天延长的血液滤过(Extended daily hemofiltration,EDHF)(每天治疗8-12小时)对脓毒性AKI患者肾功能恢复和死亡率的影响。方法:回顾性分析145例2009年4月-2013年5月接受RRT脓毒性AKI患者。患者采用CVVHF或EDHF模式治疗,统一使用聚砜膜透析器及碳酸氢盐置换液。判断预后的终点事件为28天肾功能恢复率及死亡率。结果:65例患者采用CVVHF治疗,80例患者采用EDHF治疗。CVVHF组的患者肾功能恢复率显著增加(CVVHF组:50.77%,EDHF组:32.50%,P= 0.026)。CVWHF组患者平均肾功能恢复时间为17.26天,EDHF组患者平均肾功能恢复时间为25.46天(P=0.039)。CVVHF组和EDHF组28天死亡率相似,分别是44.62%和46.25%(P=0.844)。55.38%CVVHF和28.75%EDHF组的患者RRT中发生低磷血症(P=0.001)。其它相关RRT的并发症在两组间无差异。包含临床各相关变量的多因素分析发现,CVVHF治疗是有利于肾功能恢复的独立影响因素(HR=3.81,95%可信区间为1.90-7.62,P0.001),但CVVHF治疗不是死亡的影响因素(HR=0.81,95%可信区间为0.30-1.81,P= 0.312)。结论:CVVHF治疗的患者肾功能恢复率明显增加,CVVHF及EDHF治疗的患者28天死亡率相似。
[Abstract]:The first part of the patients with septic shock and clinical analysis of death risk assessment objective: septic shock (Septic shock) and multiple organ dysfunction syndrome (MODS Multiple organ dysfunction syndrome) is a major cause of death in critically ill patients, many patients can get treatment and death in the early stage. This chapter studies the risk analysis and the integration of clinical data, to explore the clinical evaluation index the risk of death in patients with septic shock. Methods: the clinical data from January 2009 to December 2014 in 198 cases of patients with septic shock. According to the distribution of the time of death of patients, the patients were divided into early death group (died within 5 days), the late death group (died within 6-28 days) and survival group (28 days survival). Compared three groups of patients with general characteristics, clinical and laboratory parameters, analysis of parameters related to mortality and death time; inquiry Independent risk factors of causing death, thus constructing death risk model, ROC curve to verify its applicability. Results: compared to the late death and survival in patients with early death in patients with low systolic blood pressure (P0.001), low diastolic blood pressure (P0.001), low white blood cell (P=0.011), albumin (P=0.009) and low pH significantly reduced (P0.001) acute renal injury and death of patients within.28 days (Acute kidney injury, AKI) (P=0.037) (P=0.042), diabetes mellitus, coronary heart disease (P=0.049) and mechanical ventilation (P0.001) was significantly higher than that of survival. Compared to the survivor, died within 28 days with low temperature in the shock (P0.001), high frequency (P=0.010), uric acid (P=0.002), activated partial thromboplastin time prolonged (activatedpartial thromboplastin time, APTT) (P=0.001), lactic acid (P0.001) and acute physiology and chronic health increased significantly Situation assessment (Acute physiology and chronic health evaluation, APACHE II) (P0.001) and sequential organization (sequential organ failure assessment failure assessment score (P0.001), SOFA); Cox multivariate analysis showed that serum uric acid (HR=1.001, P= 0.037), pH value (HR=0.089, P0.001, APTT (HR=1.012). P=0.001) and blood lactate levels (HR=1.088, P=0.016) were independent influential factor. The death of patients with combined with the above 4 parameters set up death risk model, ROC curve proved: area under the curve of death risk model (AUC) was 0.726, the sensitivity of 76.5%, specificity of 59.2, better than the SOFA score (AUC = 0.671, the sensitivity was 68.6%. 54.1% specificity) and APACHE score (AUC = 0.630, sensitivity 68.6%, specificity 54.1%). Conclusion: septic shock occurs obvious hypotension, low white blood cells, hypoalbuminemia and rapid decompensation acidosis patients Who may be at risk of early death stage, and low temperature, high frequency, high uric acid, APTT prolonged, high lactic acid and significantly increased APACHE and SOFA II score indicates the severity of the disease; combined with AKI, diabetes, coronary heart disease and the need for mechanical ventilation in patients with death risk to blood uric acid, pH value; APTT, and blood lactate and establish the risk model have effect on the prediction of death in patients with septic shock. Second patients with septic shock and renal replacement therapy to explore Objective: To compare the timing of renal replacement treatment (Renal replacement treatment, RRT) and the general characteristics of non RRT patients, the clinical and laboratory parameters, application of observation RRT in the treatment of septic shock in the RRT impact assessment on the prognosis of RRT patients; analysis of differences between death and survival in patients with clinical parameters of patients with septic shock, RRT start time on patients Effect of prognosis. Methods: in the first part of 198 cases of patients with septic shock, 87 patients with RRT, 111 patients without RRT, analysis of two groups of patients with 28 day mortality and death time difference between the clinical and laboratory parameters, analysis of RRT effect on the prognosis in multivariate Cox proportional hazard model correction; analysis of death and survival in patients with clinical and laboratory parameters for RRT, based on the parameters and AKIN grading were statistically significant, RRT to the starting time of shock, the patients were divided into different levels, stratified analysis between patients with mortality and survival. Results: early mortality in patients with RRT was significantly lower than that of RRT who (P0.001), but the two groups were similar to the 28 day mortality rate (P=0.738); compared with non RRT patients, RRT patients with AKI (P0.001), more tumor (P=0.038) and coronary heart disease (P=0.021) and congestive heart failure (P=0.049), more than hand For patients with RRT (P=0.005); RRT APACHE score was significantly higher than that in non RRT patients (P0.001); Cox multivariate analysis showed that RRT is beneficial to the recovery of the patients factors (beta =-1.125, HR=0.325,95% CI 0.182-0.580, P0.001). The stratified analysis showed that as the pH value decreased (r=-3.840. P0.001) and APACHE II (r=3.793, P0.001) increased and SOFA scores (r=7.143, P0.001), the mortality rate increased; septic shock occurred after the beginning time of RRT was positively correlated with the death of 28 days (r=3.369, P=0.001); shock occurred delayed to the beginning time of RRT are independent risk factors of death in patients with beta (=0.540, HR=1.175, P=0.031). Conclusion: septic shock for RRT patients with more severe RRT, is conducive to the treatment of patients with recovery; for RRT, the pH value decreased significantly and APACHE II and SOFA score increased in patients with poor prognosis; shock After an early start RRT is conducive to improve the prognosis of the patients. The third part: the effect of renal replacement therapy on prognosis of septic acute kidney injury Objective: septic AKI therapy, continuous renal replacement therapy (Continuous renal replacement treatment, CRRT is superior to intermittent renal replacement therapy (Intermittent renal replacement treatment, IRRT). It is still not clear. We compared the continuous veno venous hemofiltration (Continuous venovenous hemofiltration, (CVVHF) for more than 72 hours a day) and prolonged hemofiltration (Extended daily hemofiltration, (EDHF) for 8-12 hours a day) on renal function in patients with AKI septic recovery and mortality. Methods: a retrospective review analysis of 145 cases of septic AKI patients receiving RRT April 2009 -2013 year in May. Patients with CVVHF or EDHF mode of treatment, uniform use of Polysulfone Dialyzer and bicarbonate replacement fluid. End point events prognosis 28 days for recovery of renal function and mortality. Results: 65 cases were treated by CVVHF, the rate of recovery was significantly increased in patients with renal function in 80 patients treated by EDHF.CVVHF group (group CVVHF 50.77%, group EDHF: 32.50%, P= 0.026) the average renal function.CVWHF group of patients recovered for 17.26 days, the average recovery time of renal function in EDHF patients was 25.46 days (P=0.039) of.CVVHF group and EDHF group in the 28 day mortality was similar, were 44.62% and 46.25% (P=0.844) of hypophosphatemia.55.38%CVVHF and 28.75%EDHF patients in group RRT (P=0.001). Other related RRT without complications the difference between the two groups. The clinical variables including multiple factors analysis showed that CVVHF treatment is independent factors conducive to the recovery of renal function (HR=3.81,95% CI 1.90-7.62, P0.001), but CVVHF treatment is not death The influencing factors (HR=0.81,95% confidence interval 0.30-1.81, P= 0.312). Conclusion: the recovery rate of renal function of CVVHF patients is significantly increased, and the 28 day mortality rate of CVVHF and EDHF patients is similar.

【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R459.7

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